We propose to investigate the kinetics and ultrastructure of megakaryocyte maturation under a number of experimental conditions: 1) humoral stimulation without concomitant alteration of circulating platelet levels; 2) during and after hypoxia, when production of red cells is respectively stimulated and suppressed; and 3) in vitro culture systems. In addition, we will investigate the effect of altered host platelet levels in the behavior of transplanted pluripotential stem cells from different sources. For in vivo analyses, megakaryocyte, size, ploidy, and maturation rate will be measured and accompanying changes in platelet size and number will be determined. Electron microscopy and cytochemistry will be used to elucidate morphological changes under various conditions; morphometric analysis of megakaryocytes and platelets will be done to quantitate differences. Emphasis will be placed on determining conditions under which megakaryocytes will mature in cultures. Both soft agar and liquid culture media will be employed. Ultrastructural morphology, as well as currently accepted cytochemical stains, will be used as criteria of differentiation.